Upregulated MicroRNA-25 Mediates the Migration of Melanoma Cells by Targeting DKK3 through the WNT/β-Catenin Pathway

被引:39
作者
Huo, Jia [1 ]
Zhang, Yanfei [1 ]
Li, Ruilian [1 ]
Wang, Yuan [1 ]
Wu, Jiawen [1 ]
Zhang, Dingwei [1 ]
机构
[1] Xi An Jiao Tong Univ, Dept Dermatol, Hosp 2, Xian 710004, Peoples R China
关键词
miR-25; DKK3; melanoma; CANCER; EXPRESSION; INVASION; WNT; PROLIFERATION; PROGRESSION; AUTOPHAGY; MOTILITY;
D O I
10.3390/ijms17111124
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Previous research indicates that microRNA-25 (miR-25) regulates carcinogenesis and the progression of various cancers, but the role of miR-25 in melanoma remains unclear. We observed that miR-25 was significantly upregulated in melanoma cell lines and tissue samples. Downregulation of miR-25 markedly suppressed invasion and proliferation of melanoma cells in vitro; however, overexpression of miR-25 markedly increased melanoma cell invasion and proliferation. Moreover, we observed Dickkopf-related protein 3 (DKK3) as a direct target of miR-25 in vitro. Upregulation of DKK3 partially attenuated the oncogenic effect of miR-25 on melanoma cells. Ectopic expression of miR-25 in melanoma cells induced beta-catenin accumulation in nuclear and inhibited TCF4 (T cell factor 4) activity, as well as the expression of c-Myc and Cyclin D1. In a nude xenograft model, miR-25 upregulation significantly increased A375 melanoma growth. In summary, miR-25 is upregulated in melanoma and promotes melanoma cell proliferation and invasion, partially by targeting DKK3. These results were indicated that miR-25 may serve as a potential target for the treatment of melanoma in the future.
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页数:12
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